Background and purpose: In this study, we applied an induced pluripotent stem cell (iPSC)-based model of inherited erythromelalgia (IEM) to screen a library of 295 small molecules aiming to identify candidate pain-modulating compounds. Experimental approach: Human iPSC-derived nociceptor-like cells, which exhibit action potentials in response to noxious stimulation, were evaluated using whole-cell patch-clamp and microelectrode array (MEA) techniques. Key results: Nociceptors derived from individuals with IEM showed spontaneous electrical activity characteristic of genetic pain disorders. The drug screen identified four compounds (AZ106, AZ129, AZ037, and AZ237) that significantly decreased spontaneous firing with minimal toxicity. The calculated IC50 values indicate the potential efficacy of these compounds. Electrophysiological analysis confirmed the compounds’ ability to reduce action potential generation in IEM patient-specific iPSC-derived neurons. Conclusions and implications: This high-throughput approach demonstrates the reproducibility and effectiveness of human neuronal disease modelling, offering a promising avenue for discovering new analgesics. These findings address a critical gap in current therapeutic strategies for both general and neuropathic pain, warranting further investigation. This study highlights the innovative use of patient-derived iPSC neuronal models in pain research and emphasises the potential for personalised medicine in developing targeted analgesics.